This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To investigate genes controlling the timing of puberty. Understanding the mechanism of puberty in the brain is important, as some diseases and behavioral disturbances occur in association with puberty. In this study the role of kisspeptin in the pubertal increase in LHRH release was examined. The results suggest that kisspeptin-54 release in the stalk-median eminence measured by a microdialysis method was pulsatile and mean kisspeptin-54 levels and pulse frequency, but not pulse amplitude, increased at the onset of puberty. Moreover, the pubertal increase in kisspeptin-54 release was independent from the pubertal changes in circulating ovarian estrogen, as the pubertal increase in kisspeptin-54 release was also observed in ovariectomized females. Finally, developmental changes in GPR54 sensitivity to KP were examined by assessing the LHRH response to a KP agonist and antagonist, KP-10 and peptide 234, respectively. Preliminary results suggest that the LHRH response to neither KP-10 nor peptide 234 was different between prepubertal and pubertal groups, indicating that GPR54 sensitivity does not undergo developmental changes. Collectively, the results are consistent with the hypothesis that kisspeptin plays a role in puberty. This research used WNPRC Animal Services and Assay Services. PUBLICATION: Roseweir, A.K., Kauffman, A.S., Smith, J.T., Guerriero, K.A., Morgan, K., Pielecka-Fortuna, J., Pineda, R., Gottsch, M.L., Tena-Sempere, M., Moenter, S.M., Terasawa, E., Clarke, I.J., Steiner, R.A., and Millar, R.P. Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J. Neurosci. 29:3920-3929, 2009. PMID: 19321788